Abstract
Currently there is a clear trend towards the establishment of virus-like particles (VLPs) as a powerful tool for vaccine development. VLPs are tunable nanoparticles that can be engineered to be used as platforms for multimeric display of foreign antigens. We have previously reported that VLPs derived from rabbit hemorrhagic disease virus (RHDV) constitute an excellent vaccine vector, capable of inducing specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes. Here, we evaluate the ability of chimeric RHDV VLPs to elicit immune response and protection against Foot-and-Mouth disease virus (FMDV), one of the most devastating livestock diseases. For this purpose, we generated a set of chimeric VLPs containing two FMDV-derived epitopes: a neutralizing B-cell epitope (VP1 (140–158)) and a T-cell epitope [3A (21–35)]. The epitopes were inserted joined or individually at two different locations within the RHDV capsid protein. The immunogenicity and protection potential of the chimeric VLPs were analyzed in the mouse and pig models. Herein we show that the RHDV engineered VLPs displaying FMDV-derived epitopes elicit a robust neutralizing immune response in mice and pigs, affording partial clinical protection against an FMDV challenge in pigs.
Highlights
Virus-like particles (VLPs) are macromolecular assemblies with well-defined geometry that mimic the overall structure of the native virions, while lacking any viral genome [1,2]
We have reported that dendrimeric peptides, including two or four copies of the B-cell epitope linked to the T-cell epitope, elicit potent humoral and cellular specific responses, conferring solid protection to viral challenge in pigs [33,34,35], while juxtaposition of the same two epitopes in a linear peptide is significantly less efficient [36], confirming that multimerization is an important strategy to trigger an efficient immune response based on both Foot-and-Mouth disease virus (FMDV) epitopes
The immune response and protection conferred by a chimeric VLP was assessed using eight 9-week-old white cross-bred Landrace female pigs (Agropardal SA breed) which were free of antibodies to FMDV
Summary
Virus-like particles (VLPs) are macromolecular assemblies with well-defined geometry that mimic the overall structure of the native virions, while lacking any viral genome [1,2]. We have reported that dendrimeric peptides, including two or four copies of the B-cell epitope linked to the T-cell epitope, elicit potent humoral and cellular specific responses, conferring solid protection to viral challenge in pigs [33,34,35], while juxtaposition of the same two epitopes in a linear peptide is significantly less efficient [36], confirming that multimerization is an important strategy to trigger an efficient immune response based on both FMDV epitopes With this in mind, in this report we evaluated the ability of RHDV VLPs as a vaccine vector for the induction of immune responses and protection against FMD.
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